A number of factors must be considered when developing an appropriate form of an active pharmaceutical ingredient (API) for formulation for administration to human subjects. These include efficacy, toxicity, stability, solubility/dissolution and acidity/basicity. Different formulations comprising a number of different forms of the API are usually evaluated. The outcomes of such evaluations are unpredictable.
Solubility/dissolution, stability and acidity/basicity can be very important factors to control for an API. Solubility/dissolution must be at an appropriate level to enable delivery of a sufficient dose of the active ingredient to have the desired therapeutic effect in a patient. The solubilities of different salt forms of a therapeutic agent are unpredictable.
The stability of an API must be sufficient to ensure that the product is shelf stable for long periods. Acidity/basicity is of importance for orally administered drugs and inhaled drugs as overly acidic formulations may cause discomfort to subjects upon administration.
RPL554 (9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one) is a dual PDE3/PDE4 inhibitor and is described in WO 00/58308. As a combined PDE3/PDE4 inhibitor, RPL554 has both anti-inflammatory and bronchodilatory activity and is useful in the treatment of respiratory disorders such as asthma and chronic obstructive pulmonary disease (COPD). The structure of RPL554 is shown below.

Owing to its applicability in the treatment of respiratory disorders, it is often preferable to administer RPL554 by inhalation. Franciosi et al. disclose a solution of RPL554 in a citrate-phosphate buffer at pH 3.2 (The Lancet: Respiratory Medicine November 2013; 1(9):714-27. DOI: 10.1016/S2213-2600(13)70187-5). The preparation of salts of RPL554 has not been described.